Chemoprevention for prostate cancer: the prostate cancer prevention trial
Article first published online: 21 AUG 2003
Volume 92, Issue 4, pages 339–340, September 2003
How to Cite
Fitzpatrick, J.M. (2003), Chemoprevention for prostate cancer: the prostate cancer prevention trial. BJU International, 92: 339–340. doi: 10.1046/j.1464-410X.2003.04386.x
- Issue published online: 21 AUG 2003
- Article first published online: 21 AUG 2003
With the recent publication of the Prostate Cancer Prevention Trial (PCPT) results  urologists may perhaps be at a new point in the treatment of prostate cancer, i.e. the possibility that if men take a pharmaceutical agent, fewer will require treatment for this condition. The question is now whether or not to use chemoprevention  in an effort to reduce the incidence of an increasingly common cancer .
The PCPT reported a statistically significant 24.8% risk reduction in the prevalence of biopsy-confirmed prostate cancer in patients given finasteride over a 7-year period, compared with placebo (P < 0.001); this was the primary endpoint of the trial . Allied to this finding, patients given finasteride also benefited from decreased urinary symptoms and events related to BPH. While the incidence of prostate cancer was lower, patients given finasteride were more likely to have Gleason grade 7–10 tumours, which was a secondary endpoint. Based on this evidence, should patients with BPH or at risk of prostate cancer receive finasteride as a chemoprevention therapy?
The PCPT was designed to answer this question and resulted in a clear risk reduction compared with placebo after 7 years of finasteride therapy. In such an instance not only would these patients benefit from better treatment of the BPH  but they would also reduce their risk of developing prostate cancer in the long-term.
The incidence of prostate cancer in the placebo group was 24.4%, compared with 18.4% in the finasteride group, which is a 24.8% reduction in the relative risk and a reduction in the absolute risk of 6%. This may be an artefact relating to both study design and over-reporting by clinical investigators. Patients in the trial were having regular medical examinations, and thus investigators would have been sensitive to any change in PSA levels or other surrogate markers used in the PCPT. However, any increase in the placebo group would more than likely have been allied to an increase in the number of biopsy-confirmed cases reported in the finasteride arm, and thus the absolute difference between the two treatment groups would have been unaffected.
The increase in the percentage of high-grade tumours in the finasteride group requires further investigation, considering that 97% of the cancers diagnosed were organ-confined. To clarify this issue, it can be stated in the following way: with 1000 men aged 63 years it is estimated that after 7 years 60 of them would develop prostate cancer. Of those 60 men with prostate cancer, 18 would have high-grade disease. If the same 1000 men were treated with finasteride for 7 years, only 45 would get prostate cancer and of these, 22 would have high-grade disease .
One possible reason for this may be that finasteride could cause cellular changes in prostatic tissue, resulting in a grading bias against finasteride. Alternatively, the effect might be a result of ‘natural selection’, where mitotic cells not susceptible to finasteride will have been allowed to develop, as those sensitive to finasteride were eradicated or suppressed. It is also possible that this type of prostate cancer may simply have a different cause which has remained unidentified until now. However, it may be that changes in testosterone metabolism at an early stage of the disease might have an adverse effect on tumour growth. Nevertheless, until the exact cause for this increase in high-grade tumours is established, urologists should monitor their patients carefully for any signs of aggressive tumour growth.
The choice of whether men should receive prophylactic finasteride as a form of prostate cancer chemoprevention is less clear. In such cases an informed choice should be made by the patient, with support provided by his physician. The incidence of prostate cancer was lower irrespective of age, levels of PSA at enrolment, family history of prostate cancer, race or ethnicity. Thus, patients at high risk of prostate cancer will need to review any potential side-effects from therapy with finasteride against the reduced risk for prostate cancer reported in the PCPT, and the benefits of potentially avoiding future surgery along with its accompanying impotence and incontinence.
The side-effect profile of finasteride as examined in the PCPT is hard to assess. The main difference in sexual side-effects between the groups lies in the reduction in the volume of ejaculate, which was measured only as a ‘yes/no’ question. A more scientific way of assessing these side-effects is required.
With the publication of the PCPT results it is essential that new treatment opportunities be translated from the trial setting to clinical practice. In the case of prostate cancer chemoprevention, the primary endpoint of the PCPT was achieved, with finasteride meeting its predefined reduction in the incidence of biopsy-confirmed prostate cancer. While some very important questions remain to be answered, it would be helpful if patients were given access to the latest evidence-based medical practice. To this end, new treatment guidelines are needed to translate the PCPT results into the clinical setting and provide clear guidance to practising urologists.
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